The candidate, Honglei Chen, M.D., Ph.D., has more than two years research experience in Parkinson's disease (PD) and is currently a Research Associate at Harvard School of Public Health. Dr. Chen's research interest includes the environmental and genetic etiology of sporadic PD and that of other neurodegenerative diseases, and he plans to develop an independent academic career in this area. In this K08 proposal, Dr. Chen proposes a large prospective investigation of diet and risk of sporadic PD in the Cancer Prevention Study-ll Nutrition Cohort (CPS-IIn) and a large nested case-control study of PD with genetic polymorphisms and gene-diet interactions in the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). In the CPS-IIn, he will prospectively examine among 162,408 US men and women associations of PD with dietary intakes, focusing on folate, coffee, dietary antioxidants, fat, alcohol, and dairy products. Confirmation of incident PD cases in CPS-IIn is ongoing and they expect to document 550 definite and probable PD cases diagnosed between 1992 and 2001. In the HPFS and NHS cohorts, he will evaluate the associations of PD risk with common polymorphisms of NAT2, CYP1A2, ADH2, ADH3, ADH4, and MTHFR. He also will, for the first time, explore gene-diet interactions in PD etiology, including NAT2, CYP1A2 and caffeine intake; ADH2, ADH3, ADH4, and alcohol intake; and MTHFR and folate intake. Through the year of 2000, they have documented 567 definite and probable PD cases and 454 of them provided either blood or cheek cells for genetic analysis. In this proposed nested case-control study, two controls will be selected for each PD case matching on age and gender. All three cohorts included in this proposal are well-established large prospective cohorts with comprehensive (baseline and updated) and validated dietary assessments and rigorous outcome ascertainments. Moreover, the scope of this study makes it one of the largest investigations to date. The completed or nearly completed data collection will further make this study most cost-effective. Therefore, this K08 grant will simultaneously accomplish two important goals: helping Dr. Chen develop the skills to become an independent researcher in the epidemiology of neurological diseases and furthering our understanding of the complex interrelationships among diet, genes and PD etiology. [unreadable] [unreadable]